Unique pharmacology

Alvesco^® is an inhaled corticosteroid (ICS) with a unique pharmacology which can help optimize the treatment of asthma (Figure 1).

Figure 1: Alvesco^® has a unique pharmacological profile

•  Administered as a prodrug, Alvesco^® exhibits low oropharyngeal deposition² and a high lung deposition of 52%, of which 55% is distributed to the small airways.¹
  
  
• Alvesco^® is highly lipophilic and is absorbed quickly by lung epithelial cells,³ where it is converted to the active metabolite desisobutyryl-ciclesonide (des-CIC),⁴ which reduces inflammation.
  
  
• The small particle size of Alvesco^® enables it to enter the small airways,^1,10 where it may improve small airway function.^11,12 Alvesco^® has also been shown to improve measures of large airway function.¹³
  
  
• Des-CIC forms reversible lipid conjugates in the lung, creating a reservoir capable of releasing active metabolite and prolonging the anti-inflammatory effects of Alvesco^®. Together with lipophilicity this allows for once-daily-dosing.⁸
  
  
• The low availability of Alvesco^® outside the lungs, along with rapid clearance of the drug and high protein-binding, limit the systemic activity of Alvesco^®.^5,7,9,14

 

References:

1. Newman S, Salmon A, Nave R, et al. High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma. Respir Med 2006;100:375-384
2. Richter K, Kanniess F, Biberger C, et al. Comparison of the oropharyngeal deposition of inhaled ciclesonide and fluticasone propionate in patients with asthma. J Clin Pharmacol 2005;45:146-152
3. Nonaka T, Nave R, McCracken N, et al. Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549). BMC Pharmacol 2007;7:12
4. Mutch E, Nave R, McCracken N, et al. The role of esterases in the metabolism of ciclesonide to desisobutyryl-ciclesonide in human tissue. Biochem Pharmacol 2007;73:1657-1664
5. Nave R, Bethke TD, van Marle SP, Zech K. Pharmacokinetics of [14C]ciclesonide after oral and intravenous administration to healthy subjects. Clin Pharmacokinet 2004;43:479-486
6. Stoeck M, Riedel R, Hochhaus G, et al. In vitro and in vivo anti-inflammatory activity of the new glucocorticoid ciclesonide. J Pharmacol Exp Ther 2004;309:249-258
7. Rohatagi S, Krishnaswami S, Pfister M, et al. Model-based covariate pharmacokinetic analysis and lack of cortisol suppression by the new inhaled corticosteroid ciclesonide using a novel cortisol release model. Am J Ther 2005;12:385-397
8. Nave R, Meyer W, Fuhst R, et al. Formation of fatty acid conjugates of ciclesonide active metabolite in the rat lung after 4 week inhalation of ciclesonide. Pulm Pharmacol Ther 2005; 18:390-396
9. Alvesco^® EU SmPC
10. Leach CL, Bethke TD, Boudreau RJ, et al. 2-D and 3-D imaging show ciclesonide has high lung deposition and peripheral distribution: a nonrandomized study in healthy volunteers. J Aerosol Med 2006;19(2):117-126
11. Cohen J, Douma WR, ten Hacken NH, et al. Ciclesonide improves measures of small airway involvement in asthma. Eur Respir J 2008;31:1213-20
12. Hoshino M. Comparison of effectiveness in ciclesonide and fluticasone propionate on small airway function in mild asthma. Allergol Int 2010;59:59-66
13. Vogelmeier CF, Hering T, Lewin T, et al. Efficacy and safety of ciclesonide in the treatment of 24,037 asthmatic patients in routine medical care. Respir Med 2011;105:186-94
14. Derom E, Van De Velde V, Marissens S, et al. Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5' monophosphate in asthmatic patients. Pulm Pharmacol Ther 2005;18:328-336